Escalating societal concern over the risks of exposure to extremely low frequency (ELF) electromagnetic fields has been fueled by epidemiologic studies which correlate increased incidence of leukemia or birth defects with proximity to power distribution systems. Unfortunately, the phenomenologic nature of these studies make it difficult to differentiate the pathogenic potential of electromagnetic fields from interacting factors (e.g., socioeconomic) that might as well explain an accelerated rate of disease. Conflicting reports at the basic science level have polarized the scientific community on this issue, resulting in only a weak acknowledgement of any potential hazards of 60 Hz electromagnetic exposure. Fundamentally, it is not yet clear if ELF, low intensity field exposure can modulate cell behavior, and if so whether specific characteristics of the field (frequency, intensity, duration) will differentially affect the response. Further, it is not known if a cell's interaction with the field is selective; whether fields perturb the activity of some cell types while remaining innocuous to others. To establish the extent to which ELF electromagnetic fields can influence cell behavior, it is essential to conduct a systematic, controlled study in which well defined (in both biological and physical terms) cell types are exposed to uniform fields of known frequency, intensity and duration, and the subsequent cellular response quantified. The objective of this four year study is to isolate those specific aspects of ELF electric fields (frequency, intensity, duration) which modulate cell behavior, and to identify the biophysical and morphologic properties of a cell which will promote its susceptibility to this exposure. Our preliminary results, at both the in vivo and in vitro level, demonstrate that extremely low intensity (less than 100 mu V/cm), frequency specific (10-100 Hz) electric fields can be a potent influence on both tissue adaptation and cell activity. Importantly, these results also suggest that the field:cell interaction depends not only on the characteristics of the field, but also on the size, shape, and surface characteristics of the cell which is being exposed. Ironically, it may well be this morphologic specificity which is responsible for the inconsistent and disparate reports of electric field interactions with biologic systems. We propose that the capacity of an electric field to modulate cell behavior is dependent not only on the frequency and strength of the field, but that the interaction is strongly dependent on the physical properties of the cell which is exposed. These experiments will be performed in an in vitro system in which the intensity of the induced electric field is both uniform and carefully controlled. Representative cell types of specific size, shape and surface properties will be examined. Biochemical and morphologic assays will be used to quantify electric field interactions.